Expression profiles of NPHP1 in the germ cells in the semen of men with male factor infertility

Summary NPHP1, the gene that encodes the protein nephrocystin‐1 has been identified to be mutated in Juvenile Nephronophthisis, an autosomal recessive cystic kidney disorder which is the most frequent genetic cause of end‐stage renal disease (ESRD) in children and young adults. Nphp1‐targeted mutant mice studies have shown that it did not express renal manifestations of nephronophthisis; instead male mice were infertile with oligoteratozoospermia signifying the crucial role of Nphp1 in relation to murine spermatogenesis. Whether an aberrant expression of NPHP1 in testis might lead to spermatogenic defects in human and ultimately male factor infertility is a possibility that have not been investigated so far. In this regard, characterization of NPHP1 in spermatozoa from fertile and infertile males was carried out by employing RT‐PCR, western blotting, and immunofluorescence analysis. In all the 23 normozoospermic samples we screened, NPHP1 was significantly expressed at the target message and protein level and also prominent localization pattern of NPHP1 was observed at the head, midpiece, and tail segments of spermatozoa. Conversely, in majority of the 103 infertile samples we screened, aberrant pattern of NPHP1 expression was detected at the transcript and protein level and abnormal localization pattern of expression was observed in spermatozoa. Anomalies detected in infertile cases when compared with the normozoospermic controls points to the indispensable role of NPHP1 in relation to spermatogenesis. Thus, besides the decisive association with juvenile nephronophthisis, our study provides the first direct evidence that NPHP1 is associated with male factor infertility and also could be a possible biomarker for the assessment of male fertility status.